Patients with cerebral palsy, multiple sclerosis, spinal cord trauma and other neurological illnesses have abnormalities of motor control and are frequently disabled by symptoms of spasticity. The mechanisms underlying the abnormal control of movement and abnormal reflexes are unknown, however many of the symptoms may be secondary to the removal of spinal cord inhibitory interneurons from supraspinal control. For the past 18 months we have investigated the problem and have found the following: 1) After spinal cord transection rats are initially flaccid and develop urinary retention. Over the next one to two months the animals develop signs of spasticity with increased extensor tone, increased reflexes, extensor and flexor spasms and spastic bladders. 2) During the flaccid stage, indices of the function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), are increased in spinal cord suggesting excessive activity of GABAergic interneurons during this period. 3) During the spastic phase, indices of the function of the inhibitory neurotransmitter glycine are decreased suggesting underactivity of the inhibitory glycinergic interneurons in spasticity. 4) Finally, we have evidence that the neurotransmitter of the cells projecting from motor cortex to the spinal cord utilize the excitatory amino acid, glutamate as their neurotransmitter. We plan to extend these studies to obtain a more detailed time course of the development of the biochemical changes in spinal cord and to determine their relationship to the development of abnormal reflexes. Furthermore, we plan to measure biochemical changes in spinal cord after lesions of specific areas of brain which are known to influence spinal cord. Finally, we will initiate studies to investigate the role of glutamic acid in spinal cord function and spasticity.